不同免疫检查点抑制剂相关心脏毒性的文献病例分析  

Literature case analysis on cardiotoxicity associated with various immune checkpoint inhibitiors

作　　者：李宗云 焦甲勋 高玲娜 赵越 吕琛 朱小丽 种宝贵 张春宝 郑群 LI Zongyun;JIAO Jiaxun;GAO Lingna;ZHAO Yue;LYU Chen;ZHU Xiaoli;CHONG Baogui;ZHANG Chunbao;ZHENG Qun(Department of Clinical Pharmacy,People's Hospital of Hengshui,Hengshui,Hebei 053000,China;Department of Oncology,People's Hospital of Hengshui,Hengshui,Hebei 053000,China;Department of Pharmacy,People's Hospital of Hengshui,Hengshui,Hebei 053000,China;Department of Medical Oncology,People's Hospital of Hengshui,Hengshui,Hebei 053000,China;Department of Cardiology,People's Hospital of Hengshui,Hengshui,Hebei 053000,China)

机构地区：[1]衡水市人民医院临床药学科,河北衡水053000 [2]衡水市人民医院肿瘤科,河北衡水053000 [3]衡水市人民医院药学部,河北衡水053000 [4]衡水市人民医院肿瘤内科,河北衡水053000 [5]衡水市人民医院心内科,河北衡水053000

出　　处：《安徽医药》2025年第4期833-839,共7页Anhui Medical and Pharmaceutical Journal

基　　金：河北省医学科学研究课题计划项目(20220467)。

摘　　要：目的探讨不同免疫检查点抑制剂(immune checkpoint inhibitors,ICIs)相关心脏毒性的发生情况和特点,为临床安全用药提供参考。方法检索PubMed、Embase、CNKI、万方和维普数据库,检索时间自建库至2022年12月31日。根据入排标准进行文献筛选,收集并分析ICIs相关心脏毒性的病人临床数据。结果最终纳入文献184篇,共计病人230例。ICIs相关心脏毒性类型占比最高的为心肌疾病(148/230,64.35%)。ICIs相关心脏毒性总的中位发生时间为4.00周,细胞毒性T淋巴细胞相关抗原-4(cytotoxic T-lymphocyte-associated antigen 4,CTLA-4)抑制剂的相关心脏毒性中位发生时间为11.07周,晚于抗体抑制程序性细胞死亡蛋白-1(programmed cell death protein-1,PD-1)抑制剂的3.64周(H=7.71,P=0.033)和联合用药的2.86周(H=10.14,P=0.009)。ICIs相关心脏毒性中有68.94%(159/230)的病例经过治疗后好转,但仍有29.79%(68/230)的病例死亡。与单独接受伊匹木单抗治疗的病人相比,联合使用伊匹木单抗和纳武利尤单抗的病人出现心脏毒性的时间更早(2.79周比12.00周,H=9.58,P=0.002),但病死率差异无统计学意义(34.38%比31.25%,χ^(2)=0.05,P=0.829)。结论ICIs相关心脏毒性具有类型多样,发生时间早,临床表现不典型和病死率高的特点,临床需要提高警惕。同时,不同种类的免疫检查点抑制剂相关心脏毒性发生时间、类型和结局方面有所不同,应采取不同应对策略。Objective To investigate the incidence and characteristics of cardiac immune-related adverse events(irAEs)in patients treated with various immune checkpoint inhibitors(ICIs),aiming to provide references for clinical drug safety.Methods A search was conducted in PubMed,Embase,CNKI,Wanfang,and VIP databases up to December 31,2022.Literature screening was performed based on inclusion criteria,and clinical data of patients with cardiac irAEs were collected and analyzed.Results A total of 184 arti-cles involving 230 cases were included.The highest proportion of ICIs-related cardiotoxicity was mainly found in myocardial diseases(148/230,64.35%).The overall median onset time for ICI-related cardiac toxicity was 4.00 weeks.The median onset time for cytotoxic T-lymphocyte-associated antigen 4(CTLA-4)inhibitor-related cardiac toxicity was 11.07 weeks,which was later than that for pro-grammed cell death protein-1(PD-1)inhibitors(3.64 weeks,H=7.71,P=0.033)and combination therapy(2.86 weeks,H=10.14,P=0.009).In cases of ICIs-related cardiotoxicity,68.94%(159/230)showed improvement after treatment,while 29.79%(68/230)died.Compared with patients who received ipilimumab alone,patients who received both ipilimumab and nivolumab experienced earlier on-set of cardiotoxicity(2.79 weeks vs.12.00 weeks,H=9.58,P=0.002),but no significant difference in mortality was observed(34.38%vs.31.25%,χ^(2)=0.05,P=0.829).Conclusions ICI-related cardiac toxicity has the characteristics of diverse types,early onset,atypical clinical manifestations,and high mortality,which should be concerned clinically.Furthermore,the onset time,type,and outcomes of cardiac toxicity vary with different ICIs,and tailored strategies should be employed.

关 键 词：免疫检查点抑制剂 心脏毒性 细胞毒性T淋巴细胞相关抗原-4 抗体抑制程序性细胞死亡蛋白-1 程序性细胞死亡配体-L1 免疫相关性不良反应 

分 类 号：R979.5[医药卫生—药品]